Most of our knowledge on the organization of the human visual cortex derives from neuroimaging studies that have localized a number of cortical areas based on their functional characteristics. These functional maps are not anchored to precise anatomical landmarks, and no real effort has been made to correlate the topography of the functional borders with local differences in cortical architecture. This is due to the difficulty of systematically comparing functional and histological images. The overall goal of the work is to correlate detailed retinotopic maps acquired by functional MRI (fMRI) with anatomical maps produced by quantifying intracortical myelination histologically. We propose to make this comparison explicit by using high resolution, non-linear surface-based methods to minimize the variability between subjects and brains ex-situ. Cortical geometry will be warped based on reliable sulcal landmarks that are identified automatically on the surface. In order to make histological data amenable to 3-D spatial transformations, we will use tested algorithms for alignment, and reconstruction to produce digital 3-D models of specimens whose surfaces contain architectonic information. In addition, the accuracy and resolution of retinotopic maps will be enhanced by employing a professional team of subjects for repeated scans and improved retinotopic stimulation proven to set off stronger responses from higher order visual areas. This proposal utilizes the combined expertise of three laboratories in neuroanatomical techniques, neuroimaging and computational methods for morphometric analysis and transformation. It is the first time that these expert methodologies are combined to create comprehensive maps of the human visual cortex. The result of the proposed project is the multimodal localization of higher visual areas in relation to macroscopic surface (sulcal) landmarks. The maps and definitions produced by this project will constitute a necessary framework for further functional and anatomical studies, as well as new studies of connectivity afforded by high resolution MRI, fMRI, and MR-DTI. PUBLIC HEALTH RELEVANCE: Computer-aided microanatomical mapping methods will be used to conduct a topographic survey of the visual cortex in the human brain. Specimens will be processed according to multiple histological protocols to reveal complementary architectonic features. Quantification of myelination and neuronal density will be the basis for the statistical delineation of structural borders which will result in a digital, surface-based and probabilistic map of cortical visual areas.